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RECURRENCE AND METASTASIS PATTERN IN ESOPHAGEAL CANCER FOLLOWING NEOADJUVANT CHEMORADIOTHERAPY AND ESOPHAGECTOMY
Ahmed A. Elkamel
*, Shamele Battan-Wraith, Kevin Wang, Timothy Harris, Evelyn V. Alexander, Mazin Abdalgadir, Jonathan Rice, Praveen Sridhar, Stephanie Worrell
The University of Arizona, Tucson, AZ
Background:Neoadjuvant therapy followed by esophagectomy is the standard treatment for esophageal cancer. Achieving a pathological complete response (pCR) after neoadjuvant chemoradiation therapy (nCRT) improves outcomes, but the recurrence and metastasis patterns in pCR versus residual disease patients are unclear. This study compares these patterns in those who had pCR versus those who did not.
Methods:This retrospective multi-institutional study of patients with esophageal cancer treated with nCRT followed by esophagectomy between 2008 and 2023. Patients were divided into those who had pCR and residual disease groups. Patient characteristics, metastatic patterns, adjuvant therapy, and peri-operative outcomes were analyzed. Continuous variables were expressed as mean ± SD, categorical variables as counts and percentages. Independent t-tests, chi-square tests, and logistic regression were used to assess predictors of recurrence and metastasis, with p<0.05 considered significant.
Results:There were recurrences in 41% of patients (95/232), 13% (5/39) in those that had pCR vs 47% (90/193) in those with residual disease. Metastasis patterns differed between groups: liver metastasis was most common in residual disease patients (34% vs. 10%, p=0.035), thoracic metastasis occurred in 23% of the residual disease group and 7% of the pCR group (p=0.047), and peritoneal metastases were seen in 12% of patients with residual disease but were rare in the pCR group (p=0.042). Patients with residual disease also had a higher rate of metastasis to multiple sites.
Immunotherapy was more frequently given to patients with residual disease (42% vs. 18%, p<0.001). Patients receiving immunotherapy had lower recurrence rates (27.3% vs. 45.7%, p=0.014). Logistic regression identified immunotherapy as a significant protective factor against recurrence (OR=0.159, 95% CI [0.035–0.712], p=0.016).
Logistic regression showed residual disease was a strong predictor of metastasis (OR=2.65, 95% CI [1.12–6.28], p=0.027). Immunotherapy significantly reduced the risk of metastasis (OR=0.16, 95% CI [0.035–0.71], p=0.016), and greater nodal involvement was associated with a higher risk of metastasis (OR=1.82, 95% CI [1.05–3.16], p=0.033).
Conclusion:Patients with residual disease after nCRT are more likely to develop distant metastases, especially in the liver, thorax, and peritoneum. Immunotherapy is linked to reduced recurrence and improved outcomes. Further research is needed to optimize treatment strategies for patients with residual disease following nCRT.
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